Shojaei Shahla, Panjehshahin Mohammad Reza, Shafiee Sayed Mohammad, Khoshdel Zahra, Borji Mohammad, Ghasempour Ghasem, Owji Ali Akbar
Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Iran J Med Sci. 2017 Jan;42(1):32-39.
The induction of brain-derived neurotrophic factor (BDNF) expression in the hippocampus has shown to play a role in the beneficial effects of resveratrol (RSV) on the learning and memory. The BDNF gene has a complicated structure with eight 5' noncoding exons (I-IXa), each of which can splice to a common coding exon (IX) to form a functional transcript. Estrogens increase levels of BDNF transcripts in the hippocampus of rats. The aim of this study was to evaluate the effects of the phytoestrogen, RSV, on the splicing pattern of BDNF transcripts and on the pro-BDNF protein in the hippocampi of mother rats and their embryos.
RSV (60 or 120 mg/kg BW/day) was administered orally to pregnant rats from days 1 to 20 of gestation. Hippocampi of adults and embryos were dissected 24 h after the last administration of RSV. Extracts from hippocampi were subject to quantitative (q) RT-PCR and Western blotting to assess splicing pattern of the BDNF transcripts and levels of pro-BDNF protein, respectively.
RSV (120 mg/kg BW/day) caused a statistically significant increase in the expression levels of BDNF exons III, IV and IX, but not the exon I in the hippocampi of adult rats (P≤0.05). Levels of pro-BDNF protein remained unchanged in the hippocampal tissues from both adult and embryonic rats treated by RSV (60 or 120 mg/kg BW/day).
Our results showed that RSV differentially activates promoters of the BDNF gene in the hippocampus of pregnant rats, but fails to affect the pro-BDNF level neither in adult nor in the embryonic hippocampal tissues.
海马体中脑源性神经营养因子（BDNF）表达的诱导已显示在白藜芦醇（RSV）对学习和记忆的有益作用中发挥作用。BDNF基因结构复杂，有八个5'非编码外显子（I - IXa），每个外显子都可与一个共同的编码外显子（IX）拼接形成一个功能性转录本。雌激素可提高大鼠海马体中BDNF转录本的水平。本研究的目的是评估植物雌激素RSV对母鼠及其胚胎海马体中BDNF转录本的剪接模式和前体BDNF蛋白的影响。
从妊娠第1天至第20天，对怀孕大鼠口服给予RSV（60或120 mg/kg体重/天）。在最后一次给予RSV后24小时，解剖成年大鼠和胚胎的海马体。分别对海马体提取物进行定量（q）RT-PCR和蛋白质印迹分析，以评估BDNF转录本的剪接模式和前体BDNF蛋白的水平。
RSV（120 mg/kg体重/天）使成年大鼠海马体中BDNF外显子III、IV和IX的表达水平有统计学意义的增加，但外显子I无变化（P≤0.05）。RSV（60或120 mg/kg体重/天）处理的成年和胚胎大鼠海马组织中，前体BDNF蛋白水平保持不变。
我们的结果表明，RSV可差异激活怀孕大鼠海马体中BDNF基因的启动子，但对成年和胚胎海马组织中的前体BDNF水平均无影响。
